The primary focus of this laboratory is to evaluate, characterize, and quantitate the interaction of specific lipoproteins and apolipoproteins with certain cell types. By studying the effects of the lipoproteins on the lipid and lipoprotein metabolism of fibroblasts, macrophages, and hepatocytes from normal and dyslipidemic subjects, an understanding of normal lipoprotein physiology as well as the pathophysiology of the dyslipidemias will emerge. The coordinate control of cholesterol synthesis through HMG-CoA reductase, cholesteryl ester hydrolysis by both acid and neutral cholesteryl hydrolyses, and the number and affinity of the different lipoprotein receptors in cellular membranes are of central importance in our research program. Using these techniques, the lipids, lipoproteins and their cellular metabolism have been evaluated in a number of disease states: familial hypercholesterolemia, abetalipoproteinemia, Wolman disease, cholesteryl ester storage disease and Tangier disease. We have determined that adult human liver expresses distinct recognition sites for apolipoproteins A-I, E and B. By analyzing the hepatic receptors for these apoliproteins in several dyslipidemic states, distinct genetic and physiologic control of these receptors has been demonstrated. Cellular abnormalities in cholesteryl ester hydrolysis and its relation with dyslipoproteinemia has also been explored. In addition to examining perturbations in cellular recognition and metabolism of lipoproteins, potential abnormalities in the biologic function of specific lipoproteins and apolipoproteins have been evaluated. In addition, clinical studies in the treatment of a variety of inborn errors in human lipid and lipoproteins are being conducted. The medications neomycin, niacin, cholestyramine and mevinolin are currently being studied in prospective, randomized, placebo-controlled trials. The use of bone marrow transplantation has been evaluated in Acid cholesteryl ester hydrolase deficiency.